A型肉毒毒素对大鼠胃排空及相关胃肠激素影响的研究

Effect of botulinum toxin-A on gastric emptying and gastrointestinal hormone

目的观察A型肉毒毒素(Botulinumtoxin A,BTA)对大鼠胃排空及胃肠激素分泌的影响,探讨其可能的作用机制。方法选用雄性Wistar大鼠40只,随机分为四组:对照组、BTA小剂量(10u)组、中剂量(20u)组及大剂量(40u)组。给药方法均为剖腹胃窦部肌层注射。12周末,测定胃半排空时间以评价BTA对胃排空的影响,用放免法测定血浆胃动素,免疫组化方法测定胃窦局部CCK、VIP的表达。结果①12周末,中剂量组和大剂量组胃半排时间(min)分别是(161·67±23·53、200·33±44·37),显著长于对照组(86·83±22·98)(P<0·05)。②中剂量组和大剂量组血浆胃动素(pg/ml)分别是(80·56±10·43、65·99±10·50)均低于对照组(123·65±31·10),差别有统计学意义(P<0·05)。③CCK在大剂量组胃窦部肌间神经丛表达的IOD值为(139·83±37·39),与对照组(77·91±32·21)比较,差别有统计学意义(P<0·05)。VIP在中、大剂量组胃窦肌间神经丛表达的IOD值为(63·83±19·62、58·40±15·52),低于对照组(100·04±26·36),差别有统计学意义(P<0·05)。结论大鼠胃窦部肌层内注射BTA引起胃动力降低,胃排空减慢。治疗后大鼠体内胃动素、VIP含量减少,CCK含量增加,提示BTA减慢胃排空过程可能与上述胃肠激素的变化有关。

Objective To study the effect of Botulinum Toxin - A on the gastric emptying and gastrointestinal hormone. Methods Male wistar rats were divided into four groups： small dose group, middle dose group, large dose group and control group. Each rat was laparotomized injected BTA solution 0.4ml or saline 0.4ml in antrum. At the twelveth weekend, gastric semi - empty time was determined by nuclide scan and the contents of CCK, VIP and motilin in antrum was measured by immunohistochemistry method and radio- immunity method. Results At the twelveth weekend, gastric semi - empty time in middle dose group （161.67 ± 23.53 min） and large dose group（200.33 ± 44.37 min） were significantly longer than those in control group（86.83 ± 22.98 min）, （P 〈 0.05）. Plasm motilin in middle dose group（80.56 ± 10.43 pg/ml） and large dose group （65.99 ± 10.50 pg/ml） were significantly lower than those in control group （ 123.65 ± 31.10 pg/ml）, （ P 〈 0.05）. The results of immunohistochemistry revealed that IOD of the CCK expressed in antrum myenteric plexus in large dose group （ 139.83 ± 37.39） were much higher than those in control group（77.91 ± 32.21 ）, （ P 〈 0.05）. IOD of VIP positive - staining in antrum myenteric plexus in middle dose group （ 63.83 ± 19.62） and in large dose group （58.40 ± 15.52） were much lower than those in control group （ 100.04 ± 26.36）, （ P 〈 0.05）. Conclusion BTA injected in antrum smooth muscle in rats can reduce gastric empty, The changes of MTL,VIP and CCK may be associated with the decrease of gastric empty induced by BTA. These findings offer a new clue for exploring the fresh mechanism of BTA .